In MS we now know that a type of T lymphocyte “suppresses” the immune system. These so-called “regulatory” T lymphocytes (Treg: regulatory T), when defective, are an underlying cause of autoimmune diseases, particularly MS.
A protein at the origin of the autoimmune mechanism
The study leads to the discovery that this loss of immune regulation is triggered by an increase in PRDM1-Sa protein involved in immune function and that this increase in PRDM1-S triggers a dynamic interplay of multiple genetic and environmental factors, which leads to high salt absorption.
Autoimmune diseases are known to be affected by genetic and environmental factors, including vitamin D and fatty acid deficiency. In previous research, the same team found that high salt levels contribute to the development of MS. Specifically, they observed that high salt induces inflammation in CD4 T cells, a type of immune cell, and at the same time causes a loss of function of regulatory T cells.
The study uses RNA sequencing to compare gene expression in MS patients with that of healthy individuals:
- in MS patients, researchers identify upregulation, or increased expression, of a gene called PRDM1-S, also known as BLIMP-1, known to be involved in the regulation of immune function;
- PRDM1-S induces increased expression of the salt-sensitive enzyme SGK-1, leading to disruption of regulatory T cells;
- Finally, similar overexpression of PRDM1-S is observed in other autoimmune diseases, suggesting that it may be a common feature of regulatory T cell dysfunction.
What implications? The team is currently working on the development of drugs to target and reduce the expression of PRDM1-S in regulatory T cells. At the same time, the team is looking for ways to increase the function of regulatory T cells.
It is therefore a key underlying mechanism of the loss of immune regulation in MS and probably in other autoimmune diseases, which has just been deciphered. With mechanistic insight into how Treg dysfunction occurs in these human autoimmune diseases.
With the identification of new targets, including PRDM1-S and SGK-1, this opens up hope for new therapies.
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